02864nas a2200517   4500000000100000008004100001260000900042653001500051653001000066653000900076653002200085653002900107653001000136653002900146653001100175653003100186653001100217653001200228653000900240653001500249653001600264653001100280653000900291653001600300100001300316700001600329700001400345700001400359700001000373700001000383700001400393700001700407700002000424700001500444700001200459700001200471700001300483700001700496245014800513856007700661300001000738490000600748050001600754520156200770022001402332       2013                            d  c201310aAdolescent10aAdult10aAged10aAged, 80 and over10aAnti-Inflammatory Agents10aChild10aFatty Acids, Unsaturated10aFemale10aHost-Parasite Interactions10aHumans10aleprosy10aMale10aMetabolome10aMiddle Aged10aPlasma10aSkin10aYoung Adult1 aAmaral J1 aAntunes LCM1 aMacedo CS1 aMattos KA1 aHan J1 aPan J1 aCandéa A1 aHenriques MG1 aRibeiro-Alves M1 aBorchers C1 aSarno E1 aBozza P1 aFinlay B1 aPessolani MC00aMetabonomics reveals drastic changes in anti-inflammatory/pro-resolving polyunsaturated fatty acids-derived lipid mediators in leprosy disease.  uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3744420/pdf/pntd.0002381.pdf  ae23810 v7  aAMARAL 20133 a<p>Despite considerable efforts over the last decades, our understanding of leprosy pathogenesis remains limited. The complex interplay between pathogens and hosts has profound effects on host metabolism. To explore the metabolic perturbations associated with leprosy, we analyzed the serum metabolome of leprosy patients. Samples collected from lepromatous and tuberculoid patients before and immediately after the conclusion of multidrug therapy (MDT) were subjected to high-throughput metabolic profiling. Our results show marked metabolic alterations during leprosy that subside at the conclusion of MDT. Pathways showing the highest modulation were related to polyunsaturated fatty acid (PUFA) metabolism, with emphasis on anti-inflammatory, pro-resolving omega-3 fatty acids. These results were confirmed by eicosanoid measurements through enzyme-linked immunoassays. Corroborating the repertoire of metabolites altered in sera, metabonomic analysis of skin specimens revealed alterations in the levels of lipids derived from lipase activity, including PUFAs, suggesting a high lipid turnover in highly-infected lesions. Our data suggest that omega-6 and omega-3, PUFA-derived, pro-resolving lipid mediators contribute to reduced tissue damage irrespectively of pathogen burden during leprosy disease. Our results demonstrate the utility of a comprehensive metabonomic approach for identifying potential contributors to disease pathology that may facilitate the development of more targeted treatments for leprosy and other inflammatory diseases. </p>  a1935-2735